There is a paucity of information on the effects of electrical dosage in patients who receive ECT. There is marked variability in human seizure threshold, and in the treatment of major depression, stimulus intensity relative to seizure threshold appears to impact substantially on the efficacy and efficiency of ECT, as well as on cognitive side effects. We have replicated earlier results that low dose unilateral ECT (just above seizure threshold) is ineffective, with response rates of 28% and 18% in two independent samples. In contrast, bilateral ECT, in both low and high dose conditions, has resulted in a clinical response rate of ` 70%. Unilateral ECT administered at 150% above seizure threshold has produced an intermediate response rate (47%): clearly superior to low dose unilateral ECT, but inferior to bilateral ECT (low and high dose). Across unilateral and bilateral ECT conditions, higher stimulus dose appears to significantly increase the speed of clinical response. There is also now evidence that it is the degree to which electrical dose exceeds seizure threshold, and not the absolute dose given, that impacts on efficacy and side effect profiles. In recent years there has been flowing uncertainty about the relative efficacy of unilateral ECT. These new findings indicate that depending on dosage factors, the efficacy of unilateral ECT can vary markedly. The flow and ceiling for such effects are unknown, and dose- response functions for unilateral ECT need to be determined. This is of particular clinical relevance given the superiority of unilateral ECT, at traditional dose levels, in cognitive side effects. This proposed study will use a random-assignment, double-blind, four-group design in 120 patients with major depression to compare right unilateral ECT at three dosage levels: 50%, 150% and 450% above seizure threshold, with a bilateral group treated at 150% above seizure threshold serving as a standard for efficacy and side effect comparisons. The study will provide information as to which of these unilateral ECT conditions may be preferred in clinical practice, based on the tradeoff between efficacy and side effects. In determining such relations, alternative measures for ECT stimulus quantification will be evaluated, as well as new methods for dose quantification. It is hypothesized that efficacy and objective cognitive side effects will show incremental changes at each of the unilateral ECT dose levels, and that the high dose unilateral condition will be equivalent to the moderate dose bilateral condition in efficacy, but will still retain advantages with respect to side effect profiles. In examining neurobiological effects of stimulus dosing in unilateral ECT, it is hypothesized that enhanced stimulus intensity results in greater anterior (frontal) cortical changes in EEG measures, without impact on asymmetry, and in greater ictal subcortical generalization, resulting in a steeper acute prolactin surge and greater ictal and interictal global EEG delta activity. This research is designed to address the questions of where in the dosing range unilateral ECT is optimized and, when optimized, how does this treatment compare to bilateral ECT.